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. 2019 Apr 29;9:331. doi: 10.3389/fonc.2019.00331

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Copyright © 2019 Mayfosh, Baschuk and Hulett.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Effects of heparanase on immune cells and the consequences on tumor progression. (A) Heparanase from macrophages and from tumor cells increase macrophage infiltration into tumors, cytokine secretion and phagocytic ability. (B) Cells of the tumor microenvironment increase tumor cell-heparanase and increase tumor cell proliferation. (C) Heparanase enhances NK cell infiltration into tumors and consequent tumor cell clearance. (D) Tumor cell-heparanase can block NCR signaling and consequent activation of NK cells. (E) Applications of immune cell-heparanase include use in CAR T cells, dendritic cell vaccines, and viral delivery of anti-tumorigenic agents. ECM, extracellular matrix; NCR, natural killer cytotoxicity receptor; HS, heparan sulfate; CAR-T, chimeric antigen receptor-T.